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IFN regulatory factor 8 restricts the size of the marginal zone and follicular B cell pools.

Transcriptional control of marginal zone (MZ) and follicular (FO) B cell development remains incompletely understood. The transcription factor, IFN regulatory factor (IRF)8, is known to play important roles in the differentiation of early B cells. In this article, we demonstrate that IRF8 is also required for normal development of MZ and FO B cells. Mice with a conventional knockout of Irf8 (IRF8(-/-)) or a point mutation in the IRF association domain of IRF8 had increased numbers of MZ B cells. To determine the B cell-intrinsic effects of IRF8 deficiency, we generated mice with a conditional allele of Irf8 crossed with CD19-Cre mice (designated IRF8-conditional knockout [CKO]). These mice had enlarged MZ and increased numbers of MZ and FO B cells compared with controls. The FO B cells of CKO mice exhibited reduced expression of CD23 and moderately increased expression of CD21. Gene-expression profiling showed that increased B cell production in IRF8-CKO mice was associated with changes in expression of genes involved in regulation of transcription, signaling, and inflammation. Functional studies showed that IRF8-CKO mice generated normal Ab responses to T-independent and T-dependent Ags. Thus, IRF8 controls the expansion and maturation of MZ and FO B cells but has little effect on B cell function.

Pubmed ID: 21178004


  • Feng J
  • Wang H
  • Shin DM
  • Masiuk M
  • Qi CF
  • Morse HC


Journal of immunology (Baltimore, Md. : 1950)

Publication Data

February 1, 2011

Associated Grants

  • Agency: Intramural NIH HHS, Id: ZIA AI001024-05

Mesh Terms

  • Animals
  • B-Lymphocyte Subsets
  • Cell Differentiation
  • Female
  • Gene Deletion
  • Interferon Regulatory Factors
  • Lymphocyte Count
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Mutagenesis, Insertional
  • Point Mutation
  • Protein Structure, Tertiary
  • Spleen